Inclusion Criteria:
1. Provision of informed consent prior to any study specific procedures.
2. Female and/or male aged 18 to 70 years inclusive.
3. Meet the 2019 European League Against Rheumatism/American College of Rheumatology
Classification Criteria for Systemic Lupus.
4. Have moderate to severely active signs or symptoms defined as an SLE Disease Activity
Index (SLEDAI) score of at least 6 or at least one moderately to severely active
manifestation scoring B or A on British Isles Lupus Assessment Group (BILAG) Index.
5. May be taking up to 30 mg oral prednisone daily (or equivalent steroid) that has been
stable for ≥ two weeks at the Baseline Visit.
6. May be taking antimalarial treatment at any tolerated dose that has been stable for ≥
two months at the Baseline Visit.
7, May be taking one oral or injectable standard of care immunosuppressant defined as: Any
of the following medications administered for a minimum of 12 weeks prior to signing the
informed consent, and at a stable dose for a minimum of 8 weeks prior to signing the
informed consent through Day 0: (i) Azathioprine ≤200 mg/day (ii) Antimalarial (eg,
chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or
mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate
≤25 mg/week. 8. Non steroidal anti-inflammatory drugs (NSAIDS), topical or ocular steroids, or topical
or ocular calcineurin inhibitors are allowed with any dosing schedule (prn or fixed
dosing).
9. Female subjects must use 2 effective methods of avoiding pregnancy, only one of which is
a barrier method, from the time they sign consent until 12 weeks after the last dose of
study medication unless the subject is surgically sterile (e.g. bilateral oophorectomy or
complete hysterectomy), has a sterile male partner, is at least 1 year postmenopausal, or
practices sustained abstinence consistent with the subject's customary lifestyle.
Postmenopausal is defined as at least 1 year since last menses and the subject has an
elevated follicle-stimulating hormone (FSH) level greater than the threshold laboratory
value of post-menopausal at screening. Effective methods of birth control include those
listed in Appendix 12.8. Ineffective methods that should not be used are listed in Appendix
12.9. 10. All males (sterilized or non-sterilized) who are sexually active must use condom (with
spermicide where commercially available for contraception) from Day 1 until at least 12
weeks after receipt of the final dose of IP. It is strongly recommended that the female
partner of a male subject also use an effective method of contraception from Appendix 12,8
in the protocol (other than a barrier method) throughout this period. Male subjects must
not donate sperm during the course of the study and for 12 weeks after the last dose of the
investigational product.
11. Females with an intact cervix must have documentation of a normal Pap smear with no
documented malignancy or abnormalities (e.g., cervical intraepithelial neoplasia grade III,
carcinoma in situ, or adenocarcinoma in situ within 2 years prior to randomization. Any
abnormal Pap smear result documented within 2 years prior to randomization must be repeated
to confirm patient eligibility.
12. Meets all of the following tuberculosis criteria:
- - No signs or symptoms of active tuberculosis prior to or during Screening.
- - No medical history suggestive of active tuberculosis.
- - No recent contact with a person with active tuberculosis OR if there has been such
contact, referral to a physician specializing in tuberculosis to undergo additional
evaluation prior to randomization (documented comprehensively in source), and, if
warranted, receipt of appropriate treatment for latent tuberculosis at or before the
first administration of investigational product.
- - No history of latent tuberculosis prior to initial Screening visit, with the exception
of latent tuberculosis with documented completion of appropriate treatment.
13. Testing for Inclusion in the Study for those in the anifrolumab arm:
Purified Protein Derivative or Tuberculosis spot test within 12 weeks prior to or during
screening; if negative, subject is eligible. If positive or indeterminate, subject must
undergo repeat test and chest x-ray. If both negative, subject is eligible.
Coronavirus disease (COVID-19) negative polymerase chain reaction test or equivalent test
for active infection such as rapid antigen test result during screening period and no known
or suspected exposure within 2 weeks prior to screening. If there is a known or suspected
exposure, a subject must be negative upon retest obtained 2 weeks after exposure and must
remain asymptomatic for inclusion in the study.
Exclusion Criteria:
1. Involvement in the planning and/or conduct of the study (applies to all staff at the
Coordinating Clinic and/or at the study site)
2. Have already received the 2020-2021 quadrivalent influenza vaccine.
3. Receipt of any of the following:
Any live or attenuated vaccine within 8 weeks prior to signing the ICF. Administration
of killed vaccines is acceptable as long as not the influenza vaccine.
Bacillus Calmette-Guerin (BCG) vaccine within 1 year of signing the ICF. Blood transfusion or receipt of blood products within 4 weeks prior to signing the
informed consent form (ICF)
4. For patients with active or ongoing nephritis there must be two proteinuria data
points available within the last two months to confirm a stable protein/creatine ratio
as defined by no increase of > 400 mg/gm between the first and second collection.
There may be a delay of up to two weeks between screening and baseline for a repeat
protein/creatinine ratio to be performed. The criteria will apply to the most recent
two tests.
5. In the opinion of the investigator, the patient has any active, unstable
organ-threatening manifestations of SLE. At the investigator's discretion there may be
a delay of up to two weeks between screening and baseline for appropriate diagnostic
testing to confirm this criterion is not met.
6. Lactating or pregnant females or females who intend to become pregnant or begin
breastfeeding anytime from initiation of Screening until the end of the 12-week safety
follow-up period following last dose of IP.
7. Spontaneous or induced abortion, still or live birth, or pregnancy ≤4 weeks prior to
signing the informed consent form (ICF).
8. History of cancer, apart from:
Squamous or basal cell carcinoma of the skin treated with documented success of
curative therapy ≥3 months prior to Week 0 (Day 1).
Cervical cancer in situ treated with apparent success with curative therapy ≥1 year
prior to Week 0 (Day 1).
9. Recent infection requiring hospitalization or use of intravenous anti-infectives
within four weeks of signing the informed consent form or oral anti-infectives within
two weeks of baseline or known history of splenectomy.
10. Any elevation in liver function tests within two months prior to signing the informed
consent or at the Screening visit will require reflex screening for active hepatitis.
Any confirmed positive screening for hepatitis serology will be exclusionary
including:
1. Hepatitis B surface antigen (HBsAg), OR. 2. Hepatitis B core antibody (HBcAb) AND hepatitis B virus (HBV) DNA detected above
the lower limit of quantitation (LLOQ) by reflex testing by the central
laboratory at screening.
3. Positive test for hepatitis C antibody as confirmed by central laboratory.
11. Other infections:
1. Any clinical cytomegalovirus (CMV) or Epstein-Barr virus infection that has not
completely resolved within 12 weeks prior to signing the ICF.
2. Opportunistic infection requiring hospitalization or IV antimicrobial treatment
within 3 years of randomization.
3. Clinically significant chronic infection (e.g., osteomyelitis, bronchiectasis,
etc) within 8 weeks prior to signing the informed consent form (ICF) (chronic
nail infections are allowed).
12. For subjects to receive anifrolumab: any severe case of herpes zoster infection at any
time prior to Baseline, including, but not limited to, non-cutaneous herpes (ever),
herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2
years) or ophthalmic herpes involving the retina (ever). Any herpes zoster infection
that has not completely resolved within 12 weeks prior to signing the ICF. History of
positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus
core antibody.
13. Liver function tests (AST/ALT) > 2.5 X upper limit of normal for the testing
laboratory for any cause.
14. Urine dipstick >/= 2+ with reflex protein/creatinine ratio >/= 3 gm/gm. 15. White blood cells grade 2 and caused by current treatments.
21. Hypersensitivity including anaphylaxis, known history of allergy or reaction to any
component of the investigational product (IP) formulation or history of anaphylaxis to
any human gamma globulin therapy (anifrolumab group only)
22. Known history of drug or alcohol abuse considered clinically significant by the
investigator within one year of screening. 23. Major surgery within 8 weeks before signing the informed consent form (ICF) or
elective major surgery planned during the study period
